Genetic Variant ABCC6P1:n.867+12C>T (chr16-18582479-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000546162.6(ABCC6P1):n.867+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00711 in 146,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0071 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0045 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

ABCC6P1
ENST00000546162.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.498

Publications

1 publications found

Variant links:

Genes affected

ABCC6P1 (HGNC:):

ABCC6P1 links:

ABCC6P1 (HGNC:33352): (ATP binding cassette subfamily C member 6 pseudogene 1)

ABCC6P1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Variant has high frequency in the NFE (0.0103) population. However there is too low homozygotes in high coverage region: (expected more than 1, got 0).

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6P1	NR_003569.1 link	n.691+12C>T		intron_variant	Intron 6 of 9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ABCC6P1	ENST00000546162.6 link	n.867+12C>T	intron_variant	Intron 7 of 10	2
ABCC6P1	ENST00000565566.1 link	n.656+12C>T	intron_variant	Intron 6 of 8	6
ABCC6P1	ENST00000565647.7 link	n.723+12C>T	intron_variant	Intron 6 of 9	4

Frequencies

GnomAD3 genomes

AF:

0.00710

AC:

1039

AN:

146384

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00144

Gnomad AMI

AF:

0.00559

Gnomad AMR

AF:

0.00712

Gnomad ASJ

AF:

0.00511

Gnomad EAS

AF:

0.000599

Gnomad SAS

AF:

0.00491

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.00706

GnomAD2 exomes

AF:

0.00732

AC:

1118

AN:

152794

AF XY:

0.00748

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00561

Gnomad EAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.0147

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00568

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00454

AC:

3514

AN:

773560

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

1875

AN XY:

407042

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000725

AC:

AN:

22084

American (AMR)

AF:

0.00240

AC:

AN:

38674

Ashkenazi Jewish (ASJ)

AF:

0.00336

AC:

AN:

21126

East Asian (EAS)

AF:

0.00118

AC:

AN:

35738

South Asian (SAS)

AF:

0.00251

AC:

174

AN:

69446

European-Finnish (FIN)

AF:

0.00956

AC:

477

AN:

49906

Middle Eastern (MID)

AF:

0.00167

AC:

AN:

4192

European-Non Finnish (NFE)

AF:

0.00502

AC:

2484

AN:

494930

Other (OTH)

AF:

0.00400

AC:

150

AN:

37464

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.254

Heterozygous variant carriers

468

936

1405

1873

2341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00711

AC:

1041

AN:

146474

Hom.:

Cov.:

AF XY:

0.00703

AC XY:

503

AN XY:

71574

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00144

AC:

AN:

40996

American (AMR)

AF:

0.00711

AC:

105

AN:

14774

Ashkenazi Jewish (ASJ)

AF:

0.00511

AC:

AN:

3328

East Asian (EAS)

AF:

0.000600

AC:

AN:

4996

South Asian (SAS)

AF:

0.00492

AC:

AN:

4678

European-Finnish (FIN)

AF:

0.0107

AC:

109

AN:

10144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0109

AC:

704

AN:

64384

Other (OTH)

AF:

0.00802

AC:

AN:

1996

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.268

Heterozygous variant carriers

109

218

327

436

545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0161

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.0

(source)

DANN

Benign

0.31

PhyloP100

-0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over